Cardiovascular Institute, Laboratory of Molecular and Cellular Cardiology, Department of Experimental and Clinical Medicine, Magna Graecia University, Germaneto, Catanzaro, Italy.
Circ Res. 2011 Sep 30;109(8):880-93. doi: 10.1161/CIRCRESAHA.111.240150. Epub 2011 Aug 18.
MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown.
The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo.
We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression.
Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases.
微小 RNA（miR）-1 和 -133 在骨骼和心肌生物学和病理生理学中起着至关重要的作用。然而，它们在血管细胞生理学和疾病中的表达和调节目前尚不清楚。
本研究旨在评估 miR-1 和 miR-133 在体外和体内血管平滑肌细胞（VSMC）表型转换中的作用。
我们在此证明，miR-133 在体外和体内的血管平滑肌细胞（VSMC）中表达强烈，而 miR-1 的血管水平可以忽略不计。miR-133 在体外和体内对 VSMC 表型转换具有强大的抑制作用，而 miR-1 本身没有任何相关作用。miR-133 的表达受细胞外信号调节激酶 1/2 激活的调节，与 VSMC 生长呈负相关。事实上，当 VSMCs 在体外被诱导增殖时，miR-133 的表达会降低，而在体内血管损伤后，miR-133 的表达会增加，而当 VSMCs 在体外和体内被诱导回静息状态时，miR-133 的表达会增加。miR-133 的缺失和功能获得实验表明，miR-133 在 VSMC 生长中发挥了机制作用。因此，腺相关病毒-miR-133 可减少但抗-miR-133 可加剧体外和体内 VSMC 的增殖和迁移。miR-133 特异性抑制体外和体内转录因子 Sp-1 的表达，并通过 Sp-1 抑制调节平滑肌基因表达。
我们的数据表明，miR-133 是体外和体内血管平滑肌细胞表型转换的关键调节因子，提示其在血管疾病中的潜在治疗应用。
